Transport mechanisms at the blood-brain barrier were studied in the rat. An in situ brain perfusion technique was developed to examine carrier-mediated transport at the cerebral capillary endothelium. Brain perfusion with physiological saline solution or with blood did not alter cerebrovascular permeability to sucrose. Barrier permeability to nonelectrolytes was related linearly to lipid solubility. Large neutral amino acids cross the blood-brain barrier by facilitated diffusion. Cerebrovascular transport of large neutral amino acids did not change significantly in the Fischer-344 rat between 3 and 24 months of age. The cerebrovascular permeability to inorganic ions was low, comparable to permeabiliy of a cell membrane, and followed the sequence K Greater than Mg Greater than Na Greater than Cl Greater than Ca. Chloride transport across the blood brain barrier was by a saturable system which was inhibited by monovalent anions. In contrast, calcium influx into the brain was directly proportional to the plasma concentration of ionized calcium. The low permeability of the cerebrovascular endothelium to Na was maintained with age in the rat, whereas the cerebrospinal fluid transfer constant for Na fell by 18%.